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Malignant transformation of low grade astrocytomas
Thursday, /0 July /997
of nuorescein Na was intravenously injected . Tumor removal was begun some 20 minutes after the injection, when the fluorescence was observed only in the area lacking the blood-brain barrier function . The tumor was removed while the image was being switched back and forth between the ordinary microscopic image and the fluorescein image as necessary ; tumor removal was done by monitoring the fluorescent image alone. ReSUlts: Fluorescence was observed in almost the same area as that enhanced by CT or MRI in all cases . The fluorescent area was almost completely removed in all cases except for two cases of glioma of the cerebral basal ganglia and brain stem. Our histological findings revealed a large number of tumor cells and a conspicuous vascular reaction such as proliferation of endothelial cells in the fluorescein-positive area. On the other hand, the fluorescein-negative area showed necrosis, and only a small number of tumor cells and little vascular reaction were found there. Discussion and Conclusions: In the treatment of malignant glioma, optimal surgical removal is very important. Therefore , it is thought that as a rule, as much of the tumor as possible should be removed. The area enhanced by CT or MRI provides significant information in deciding the extent of removal. For determination of the area enhanced by CT during surgery, fluorescein has been used on a trial basis. Our system enables adequate removal of the tumor within a short time, and without worsening of neurological symptoms after surgery.
I P·5-541 I Malignant transformation of low grade astrocytomas GnV. Ciubotaru, AI. Constantinovici. Clinical EmergencyHospital "Prof. Dr. D.
Bagdasar" Bucharest, Romania The evolution of 12 patients with grade I astrocytoma and of 62 patients with grade II astrocytoma . all of them having a minimum postoperative Kamofski index of 60 is presented . All patients were treated by large surgical resection and chemotherapy (CCNU t 30 mg/m2 body surface). Co irradiation (50--60 Gy) was added in 8 patients (1 case with a grade I astrocytoma and 7 with grade II astrocytoma). A tumoral reccurency appea red in 4 cases of grade I astrocytoma after 1.5-3 years postoperation, From lhese, 2 cases were reoperated, for one case malignancy was increased from grade I to grade III. From the 42 patients with grade II astrocytoma 14 presented tumoral reccurency after 4 months to 4 years postoperatively (13 being from the 35 patients treated with CCNU only and 1 was treated by CCNU and irradiation). From these 14 reccurencies, 7 were reoperated and in 5 of them the malignity was found 10 be increased. There are established correlat ions between the tumoral recurrences. sex, age and tumor location .
j P-5-542 !
Correlation between choline level measured by proton magnetic resonance spectroscopy and Ki-67 labeling index in gliomas
Toshihiro Kumabe 1 • Hiroaki Shimizu 1.2. Teiii Tominaga 1 , Takashi Yoshimoto 1 • 1 Department of Neurosurgery, Tonoku UniversitySchool of Medicine, Sendai, Japan, 2 Department of Neurosurgery, Kohnan Hospital, Sendai, Japan
Introduction: We have shown that semiquantitive choline values (Cho) measured by proton magnetic resonance spectroscopy (' H MRS) is a reliable index for predicting the WHO grading of gliomas . In this study, we investigated the correlation between the Cho and the Ki-67 labeling index. In addilion , thallium-201 single photon emission computed tomog raphy (20 1 T1 SPECT) was employed to evaluate the malignancy of the tumor. Materials and Methods: Thirty glioma patients were enrolled in this study. The histolog ical diagnosis was made according to the WHO classification. Ki-67 stain ing of paraffin embedded sections with monoclonal antibody MIB-l was done using a modification of the techn ique of Shi et al. In the area with the highest number of labeled cells, the percentage of Ki-67 positive nuclei (labeling index; L1) was determined. The protocol for the semiquantitive measurement of the Cho was described previously in AJNR. 17, 737, 1996. 201T1 SPECT was performed in 18 patients four hours alte r 3 mCi of 2o' T 1 was injected. To express the 20 1 Tl uptake, the ratio of the average counts within the tumor and the homologous contralateral region was used Results and Discussion: The Cho and the Ki-67 LI could differentiate low and high grade gliomas. These parameters showed a good linear relationship when the Ki-67 LI was below 25%. However, highly malignant gliomas with a Ki-6711 of more than 25% did not have the Cho correlated with the Ki-67 L1. In these cases, 20 1 T1 uptake was useful to determine the tumor as highly malignant In conclusion, semiquant ification of the Cho by 1 H MRS and 201 T1 SPECT are complementary useful to predict the growth activity of gliomas.
Tumours of the eNS- Gliomas
S227
IP-5-543 I Expression of neural cell adhesion molecule (NCAM) in human brain and brain tumors: An inverse correlation with malignancy of astrocytic tumors Hikaru Sasaki, Kazunari Yoshida, Makoto Inaba, Mitsuh iro Otani . Takeshi Kawase. Department of Neurosurgery, School of Medicine, Keio
University. Tokyo, Japan Introduction: Cell adhesion molecules are among key factors in the malignant evolution of brain tumors. The aim of this study is to investigale the expression of neural cell adhesion molecule (NCAM) in human brain tumors and assess a relationship to the malignancy of astrocytic tumors. Methods: The expression of NCAM was examined in normal human brain and 60 brain tumors including 44 astrocytic tumors by Western blot analysis, and the degree of sialylatio n was also studied by neuraminidase digestion. As to astrocytic tumors, NCAM was quantified for each group of bands (NCAM 170--180, NCAM 145, NCAM 120-1 25), and a correlation to histology, the extent of hyperintense area on T2 weighted magnetic resonance images, presence or absence of dissemination, and proliferating cell indices (PCls) determined by MIB-1 immunohistochemistry were investigated. Results: In normal human brain, five bands of NCAM were identified (180, 170, 145, 125, 118 kD). In astrocytic tumors, the 145 kD band and the band around 120-125 kD were mainly expressed , and the 180 kD band less frequently. The degree of sialylation of NCAM in astrocytic tumors was almost identical to that of normal brain, smaller than those of neurinomas and medulloblastoma. The amount of each NCAM in astrocytic tumors has been shown to be inversely correlated with all indices of malignancy employed, and NCAM expression was barely detectable in glioblastomas and anaplastic astrocytomas either with dissemination or high PCls . Conclusions: We have provided the lirst direct evidence that NCAM is down-regulated in the development of malignant potentials of astrocytic tumors , and reduced NCAM expression mighl be involved in the malignant evolution of astrocytic tumors.
IP·5-544 I MISI immunohistochemistry and patient prognosis in cerebral astrocytic tumors
Yutaka Umebara, Minoru Jimbo, Mitsunobu Ide, Masaaki Yamamoto , 5h innji Hagiwara, Osami Kubo ' . ' Departmentof Neurosurgery, Dai-ni
Hospital, Tokyo, Japan, Neurological Institute, Tokyo Womens Medical Col/ege, Tokyo. Japan Introduction: The treatment and prognosis of patients with astrocyti c tumors are currently guided by histopathological classification. But. for some tumors, histological differentiation is not clear. The aim of this study is to evaluate immunohistochemistry using MIBl as a prognostic indicator for patients with astrocytic tumors. Methods: We examined 35 astrocyte tumors of patients whole clinical indices were well documented. There were 15 gliobastomas, 13 anaplastic astrocytomas, five astrocytomas, two pllocytlc astrocytomas. The formalin-fixed , paraffin-embedded archival tissue sections of 35 cases were immuno-stained using monoclonal antibody MIB1. The MIB1 staining index (MIB1 SI) was defined as lhe number of MIB1 positive cells divided by the total number of tumo r cells in a most viable field on the slice. Results: The MIBl Sis of 35 cases ranged from 0.6 to 39.6% (median: 15.6%), which were well correlated with grades with malignancy histological classification of WHO (p < 001 Kruskal·Wallis test). The clinical survival time of the patient was also correlated with MIBl Sis (r = - 0.89. P < 0.0001, Spearman rank correlation test). Thus, patients with less than 16% of MIB1 SI had a better prognosis in survival time than those with more than 16% (p < 0.001, logrank test). Discussion and Conclusions: It appea rs thal MIB1 51using archival paraffin-embedded samples is of value in predicting prognosis in astrocytlc tumors.
IP·5-545 I The.~nalysis of brain tumors using the MIB-1 positive rate Kazuaki Yamamoto 1, Noriaki 5ugawa " Satoshi Ueda " Hidetosh i Okabe 2 , Yoshimasa Ohshima. I Depts. of Neurosurgery, Kyoto PrefecturalUniversity of
Medicine, Kyoto, Japan. 2 Deptsof Medical Biological Laboratory, Shiga Medical University. and OhshimaHospital, Kyoto. Japan Purpose: MIB·1 positive rate is a good marker 01 proliferative actiVity in tumors. We examined whether there is a relationship between the semiquant itative value of Ki-67 mRNA by Differential Polymerase Chain Reaction and the positive percentage of MIB-1 staining in brain tumors. and we also investigated whether the percentage of MIB-1 staining in malignant gliomas might be a good prognostic factor. Material and Method: The total mRNA was extracted from 33 brain tumors (15 glioblastomas, 5 anaplastic astrocytomas , 1 astrocytoma, 1 medulloblastoma, 2 malignant lymphomas , 4 meningiomas, 5 pituitary adenomas) . We
of nuorescein Na was intravenously injected . Tumor removal was begun some 20 minutes after the injection, when the fluorescence was observed only in the area lacking the blood-brain barrier function . The tumor was removed while the image was being switched back and forth between the ordinary microscopic image and the fluorescein image as necessary ; tumor removal was done by monitoring the fluorescent image alone. ReSUlts: Fluorescence was observed in almost the same area as that enhanced by CT or MRI in all cases . The fluorescent area was almost completely removed in all cases except for two cases of glioma of the cerebral basal ganglia and brain stem. Our histological findings revealed a large number of tumor cells and a conspicuous vascular reaction such as proliferation of endothelial cells in the fluorescein-positive area. On the other hand, the fluorescein-negative area showed necrosis, and only a small number of tumor cells and little vascular reaction were found there. Discussion and Conclusions: In the treatment of malignant glioma, optimal surgical removal is very important. Therefore , it is thought that as a rule, as much of the tumor as possible should be removed. The area enhanced by CT or MRI provides significant information in deciding the extent of removal. For determination of the area enhanced by CT during surgery, fluorescein has been used on a trial basis. Our system enables adequate removal of the tumor within a short time, and without worsening of neurological symptoms after surgery.
I P·5-541 I Malignant transformation of low grade astrocytomas GnV. Ciubotaru, AI. Constantinovici. Clinical EmergencyHospital "Prof. Dr. D.
Bagdasar" Bucharest, Romania The evolution of 12 patients with grade I astrocytoma and of 62 patients with grade II astrocytoma . all of them having a minimum postoperative Kamofski index of 60 is presented . All patients were treated by large surgical resection and chemotherapy (CCNU t 30 mg/m2 body surface). Co irradiation (50--60 Gy) was added in 8 patients (1 case with a grade I astrocytoma and 7 with grade II astrocytoma). A tumoral reccurency appea red in 4 cases of grade I astrocytoma after 1.5-3 years postoperation, From lhese, 2 cases were reoperated, for one case malignancy was increased from grade I to grade III. From the 42 patients with grade II astrocytoma 14 presented tumoral reccurency after 4 months to 4 years postoperatively (13 being from the 35 patients treated with CCNU only and 1 was treated by CCNU and irradiation). From these 14 reccurencies, 7 were reoperated and in 5 of them the malignity was found 10 be increased. There are established correlat ions between the tumoral recurrences. sex, age and tumor location .
j P-5-542 !
Correlation between choline level measured by proton magnetic resonance spectroscopy and Ki-67 labeling index in gliomas
Toshihiro Kumabe 1 • Hiroaki Shimizu 1.2. Teiii Tominaga 1 , Takashi Yoshimoto 1 • 1 Department of Neurosurgery, Tonoku UniversitySchool of Medicine, Sendai, Japan, 2 Department of Neurosurgery, Kohnan Hospital, Sendai, Japan
Introduction: We have shown that semiquantitive choline values (Cho) measured by proton magnetic resonance spectroscopy (' H MRS) is a reliable index for predicting the WHO grading of gliomas . In this study, we investigated the correlation between the Cho and the Ki-67 labeling index. In addilion , thallium-201 single photon emission computed tomog raphy (20 1 T1 SPECT) was employed to evaluate the malignancy of the tumor. Materials and Methods: Thirty glioma patients were enrolled in this study. The histolog ical diagnosis was made according to the WHO classification. Ki-67 stain ing of paraffin embedded sections with monoclonal antibody MIB-l was done using a modification of the techn ique of Shi et al. In the area with the highest number of labeled cells, the percentage of Ki-67 positive nuclei (labeling index; L1) was determined. The protocol for the semiquantitive measurement of the Cho was described previously in AJNR. 17, 737, 1996. 201T1 SPECT was performed in 18 patients four hours alte r 3 mCi of 2o' T 1 was injected. To express the 20 1 Tl uptake, the ratio of the average counts within the tumor and the homologous contralateral region was used Results and Discussion: The Cho and the Ki-67 LI could differentiate low and high grade gliomas. These parameters showed a good linear relationship when the Ki-67 LI was below 25%. However, highly malignant gliomas with a Ki-6711 of more than 25% did not have the Cho correlated with the Ki-67 L1. In these cases, 20 1 T1 uptake was useful to determine the tumor as highly malignant In conclusion, semiquant ification of the Cho by 1 H MRS and 201 T1 SPECT are complementary useful to predict the growth activity of gliomas.
Tumours of the eNS- Gliomas
S227
IP-5-543 I Expression of neural cell adhesion molecule (NCAM) in human brain and brain tumors: An inverse correlation with malignancy of astrocytic tumors Hikaru Sasaki, Kazunari Yoshida, Makoto Inaba, Mitsuh iro Otani . Takeshi Kawase. Department of Neurosurgery, School of Medicine, Keio
University. Tokyo, Japan Introduction: Cell adhesion molecules are among key factors in the malignant evolution of brain tumors. The aim of this study is to investigale the expression of neural cell adhesion molecule (NCAM) in human brain tumors and assess a relationship to the malignancy of astrocytic tumors. Methods: The expression of NCAM was examined in normal human brain and 60 brain tumors including 44 astrocytic tumors by Western blot analysis, and the degree of sialylatio n was also studied by neuraminidase digestion. As to astrocytic tumors, NCAM was quantified for each group of bands (NCAM 170--180, NCAM 145, NCAM 120-1 25), and a correlation to histology, the extent of hyperintense area on T2 weighted magnetic resonance images, presence or absence of dissemination, and proliferating cell indices (PCls) determined by MIB-1 immunohistochemistry were investigated. Results: In normal human brain, five bands of NCAM were identified (180, 170, 145, 125, 118 kD). In astrocytic tumors, the 145 kD band and the band around 120-125 kD were mainly expressed , and the 180 kD band less frequently. The degree of sialylation of NCAM in astrocytic tumors was almost identical to that of normal brain, smaller than those of neurinomas and medulloblastoma. The amount of each NCAM in astrocytic tumors has been shown to be inversely correlated with all indices of malignancy employed, and NCAM expression was barely detectable in glioblastomas and anaplastic astrocytomas either with dissemination or high PCls . Conclusions: We have provided the lirst direct evidence that NCAM is down-regulated in the development of malignant potentials of astrocytic tumors , and reduced NCAM expression mighl be involved in the malignant evolution of astrocytic tumors.
IP·5-544 I MISI immunohistochemistry and patient prognosis in cerebral astrocytic tumors
Yutaka Umebara, Minoru Jimbo, Mitsunobu Ide, Masaaki Yamamoto , 5h innji Hagiwara, Osami Kubo ' . ' Departmentof Neurosurgery, Dai-ni
Hospital, Tokyo, Japan, Neurological Institute, Tokyo Womens Medical Col/ege, Tokyo. Japan Introduction: The treatment and prognosis of patients with astrocyti c tumors are currently guided by histopathological classification. But. for some tumors, histological differentiation is not clear. The aim of this study is to evaluate immunohistochemistry using MIBl as a prognostic indicator for patients with astrocytic tumors. Methods: We examined 35 astrocyte tumors of patients whole clinical indices were well documented. There were 15 gliobastomas, 13 anaplastic astrocytomas, five astrocytomas, two pllocytlc astrocytomas. The formalin-fixed , paraffin-embedded archival tissue sections of 35 cases were immuno-stained using monoclonal antibody MIB1. The MIB1 staining index (MIB1 SI) was defined as lhe number of MIB1 positive cells divided by the total number of tumo r cells in a most viable field on the slice. Results: The MIBl Sis of 35 cases ranged from 0.6 to 39.6% (median: 15.6%), which were well correlated with grades with malignancy histological classification of WHO (p < 001 Kruskal·Wallis test). The clinical survival time of the patient was also correlated with MIBl Sis (r = - 0.89. P < 0.0001, Spearman rank correlation test). Thus, patients with less than 16% of MIB1 SI had a better prognosis in survival time than those with more than 16% (p < 0.001, logrank test). Discussion and Conclusions: It appea rs thal MIB1 51using archival paraffin-embedded samples is of value in predicting prognosis in astrocytlc tumors.
IP·5-545 I The.~nalysis of brain tumors using the MIB-1 positive rate Kazuaki Yamamoto 1, Noriaki 5ugawa " Satoshi Ueda " Hidetosh i Okabe 2 , Yoshimasa Ohshima. I Depts. of Neurosurgery, Kyoto PrefecturalUniversity of
Medicine, Kyoto, Japan. 2 Deptsof Medical Biological Laboratory, Shiga Medical University. and OhshimaHospital, Kyoto. Japan Purpose: MIB·1 positive rate is a good marker 01 proliferative actiVity in tumors. We examined whether there is a relationship between the semiquant itative value of Ki-67 mRNA by Differential Polymerase Chain Reaction and the positive percentage of MIB-1 staining in brain tumors. and we also investigated whether the percentage of MIB-1 staining in malignant gliomas might be a good prognostic factor. Material and Method: The total mRNA was extracted from 33 brain tumors (15 glioblastomas, 5 anaplastic astrocytomas , 1 astrocytoma, 1 medulloblastoma, 2 malignant lymphomas , 4 meningiomas, 5 pituitary adenomas) . We